The aim of the proposed research is to pursue an investigation of esophageal clearance in health and disease with a special emphasis on its role as an important defense against reflux esophagitis. The aim of this grant will be achieved by pursuing three interrelated objectives: 1) Investigate the esophageal acid clearance mechanism in normal subjects and in esophagitis patients. Normal acid clearance has been shown to depend on both transport of the acid volume from the esophagus by peristalsis and the naturalization of acid by swallowed saliva. 2) Evaluate mechanisms for transport of a bolus through the esophagus in normal subjects and in esophagitis patients with motor dysfunction. 3) Study the intrinsic neural mechanisms controlling esophageal peristalsis in the human and the animal model. A particular emphasis of this study will be to extend our knowledge of the esophageal acid clearance mechanism to patients with reflux esophagitis and further refine our understanding of the normal clearance mechanism. With the advent of ambulatory pH monitoring systems, knowledge of acid clearance after spontaneous gastroesophageal reflux can be obtained under more physiologic conditions. Studies will be done to evaluate the salivary response to spontaneous acid gastroesophageal reflux and to define subpopulations of patients that lack this apparently protective response to esophageal acid. An important aspect of this study will be to investigate how the transport of a bolus through the esophagus relates to both the peristaltic contraction and the resulting pressure field generated within the bolus. Various physical factors, such as bolus volume and intra-abdominal pressure, will be evaluated for their effects on esophageal bolus transport. Of particular interest will be a study of how abnormalities in peristalsis relate to bolus transport in patients with reflux esophagitis. The value of this work will be enhanced engineering analysis of the fluid mechanics of esophageal bolus transport. Another major thrust of this study will be to investigate the intrinsic neural mechanisms controlling esophageal peristalsis by in vitro studies in viable human esophageal specimens obtained from kidney donors who have been declared legally brain dead. The potential role for peptide neurotransmitters in modulating esophageal peristalsis will be studied by focusing on the effects of substance P nd the opioid peptides on the esophagus in the opossum.